Single procedure indicators

ABSTRACT

Disclosed herein are single use indicators and methods for employing the same. Such indicators and their uses are directed towards identifying the discharge status of single procedure devices, which are typically, but not limited to, medical devices.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims priority to U.S. Provisional Application No.62/411,005 “Water Absorbing Polymer As Single Use Indicator For SingleProcess Reamers,” which was filed on Oct. 21, 2016, the entire contentsof which are hereby incorporated by reference in their entirety.

FIELD OF THE INVENTION

The present disclosure relates generally to single use indicators. Inparticular, the present technology concerns such indicators and theiruse in identifying the discharge status of single procedure devices,which are typically, but not limited to, medical devices.

BACKGROUND OF THE INVENTION

The following description is provided to assist the understanding of thereader. None of the information provided or references cited is admittedto be prior art.

On a global scale, health care-associated infections, i.e., nosocomialinfections, impact hundreds of millions of patients annually, whichconsequently imparts a considerable mortality rate. To this end, ofevery one-hundred hospitalized patients at any given time, seven indeveloped countries, and ten in developing countries, will acquire atleast one nosocomial infection. See World Health Organization PatientSafety, “Health Care-Associated Infections: Fact Sheet,” 2011.

Albeit endemic to all health care environments, nosocomial infectionsare nevertheless markedly higher in low and middle-income countriescompared to higher income nations, and more specifically in neonatalpatients and those requiring intensive care. See id. And, while urinarytract infection is the most frequent health care-associated infection inhigh-income countries, surgical site infection is the leading infectionin settings with limited resources, affecting up to one-third ofoperated patients in those countries. Notwithstanding the demographiccharacter of these hospital acquired afflictions, nosocomial illnessesbeget a substantial economic burden that requires further attention.

Accordingly, there has been a gradual shift in recent years fromreusable instruments that potentially harbor infectious pathogens, i.e.,to the extent that sterilization procedures break-down or areinadequate, to single procedure medical instruments which theoreticallypossess a decreased risk of transmitting nosocomial pathogens. Thepotential for reuse of single procedure devices, however, cannot beignored. Whether by mistake, misuse, or reprocessing, circumstancesremain in which single procedure devices are employed beyond theirintended lifecycle.

To a large extent, such hazardous recycling of single procedure deviceswould be curtailed by implementing a system in which one or moresingle-use indications conspicuously identify when a device is at itsend-of-use. By possessing a distinct indication—that a single proceduredevice has been discharged—the risk of mistakenly recirculating such adevice back into the operating room can be greatly reduced. Hence, thereis a current need to address the foregoing issues by developing lowcost, biocompatible, single-use medical device indicators that arereadily ascertainable to health care personnel. See, e.g., Schultz, J.B., “Disposables in the O.R. ‘Cover Story: Disposables, ECA MedicalInstruments,’” (2013).

SUMMARY

In one aspect, the present disclosure provides a method for determiningthe discharge status of a single procedure device, including (a)providing the device, where the device includes at least one indicatorregion configured to transition from an unmodified state to a modifiedstate in response to an exposure; (b) subjecting the device to theexposure after the single procedure has been performed using the device;(c) assessing the transition state of the at least one indicator region,where the modified state of the at least one indicator regionirreversibly identifies that the device has been subjected to theexposure after the single procedure; and (d) determining the dischargestatus of the device based on the transition state assessment of the atleast one indicator region, where the device is affirmatively dischargedwhen the at least one indicator region is in the modified state.

In some embodiments, the at least one indicator region includes abiocompatible composition entailing one or more of (i) at least onefiller, (ii) one or more binders, (iii) one or more additives, and (iv)a solvent, and combinations thereof. In illustrative embodiments, themethods further entail one or more of (e) labelling the affirmativelydischarged device as end-of-use, (f) segregating the affirmativelydischarged device from other single procedure devices that have not beenaffirmatively discharged, and (e) disposing of the affirmativelydischarged device.

In some embodiments, the exposure entails contacting the deviceincluding the at least one indicator region with water, where the watercontact occurs via one or more autoclave cycles, steam sterilizationcycles, sterilization procedures, simple application of water and/orsteam, aqueous disinfection, washing, and/or the sterile application ofwater or steam. In some embodiments, the exposure is one or moreautoclave steam sterilization cycles. In some embodiments, the exposurecomprises subjecting the device including the at least one indicatorregion to one or more steam sterilization cycles. In suitableembodiments, the one or more steam sterilization cycles are performedfor a duration at temperatures and pressures sufficient to (i)transition the at least indicator region from the unmodified state tothe modified state, and (ii) sterilize the device.

In some embodiments, the device is a medical device, where the medicaldevice is a single use orthopedic surgical device in some embodiments.The medical device is selected from, in certain embodiments, reamers,awls, rod benders, drill guides, guide tubes, distance gages, inserters,implant holders, clamps, portals, screwdrivers, spacers, distracters,plate benders, broaches, fusion plates, fusion screws, spinal rods,spinal connectors, artificial discs, tissue-anchoring devices, fixationdevices, Stineman pins, dilators, joint spreaders, rasps, fusion cages,Kerrisons and Rongeurs, and combinations thereof. In some embodiments,the medical device has a proximal end and a distal end, where the atleast one indicator region is located at or about the proximal end ofthe medical device.

In suitable embodiments, the at least one indicator region has abiocompatible composition including at least one filler and one or morebinders, where the at least one filler is one or more superabsorbentpolymers possessing a swelling capacity range of about 30-500 fold thevolume of the one or more superabsorbent polymers prior to beingsubjected to the exposure. In illustrative embodiments, the one or moresuperabsorbent polymers are selected from polyacrylates,polyacrylamides, polyacrylamide copolymers, polyacrylic acid, sodiumpolyacrylate, potassium polyacrylate, lithium polyacrylate, ammoniumpolyacrylate, ethylene maleic anhydride copolymer,carboxymethylcellulose, polyvinyl alcohol copolymers, polyethyleneoxide, and copolymers of polyacrylonitrile, and combinations thereof.

In illustrative embodiments, the biocompatible composition is formulatedsuch that after the biocompatible composition is applied to a proximalend of a device, i.e., constituting the indicator region, thesuperabsorbent polymer (SAP) is sterically arrange throughout theindicator region to ensure that water, when present, is able tocontact—and accordingly swell—the SAP, i.e., the water is accessible tothe SAP for adsorption via SAP surface exposure. Likewise, in someembodiments of the present invention, the SAP molecules are contiguouslyconformed or are arranged in a substantially contiguous configurationwithin the biocompatible composition, and consequently throughout theindicator region, such that water, when present, is able to continuouslypercolate the indicator region until the SAP swelling capacity isachieved.

The one or more binders of the present technology, in some embodiments,are selected from alkyds, acrylics, vinyl-acrylics, polyurethanes,polyesters, melamine, epoxies, silanes, siloxanes, and oils, andcombinations thereof. In illustrative embodiments, the methods furtherinclude one or more solvents, additives, accelerants, surfactants,emulsifiers, reducing agents, fluidizing agents, detergents, wettingagents, and dispersants, and combinations thereof. The one or moreadditives, moreover, are selected from clays, kaolin, kaolinite,halloysite, diaspore, bentonite (Fuller's earth), ball clay, commonclay, shale, fire clay, illite, chlorite, smectite minerals, quartz,limestone, silicate compounds, and quartz, and combinations thereof, incertain embodiments.

In some embodiments, the one or more solvents are selected from one ormore of non-polar solvents, polar solvents, non-aqueous solvents,aqueous solvents, protic solvents, aprotic solvents, lipophilicsolvents, hydrophilic solvents, water-miscible solvents, andwater-immiscible solvents, and combinations thereof. In illustrativeembodiments, the one or more binders are dissolved in the one or moresolvents. In some embodiments, the one or more fillers, polymers and/orsuperabsorbent polymers (SAPs) are not miscible in the solvent. Insuitable embodiments, the one or more solvents are selected from xylene,toluene, alcohols, and ketones, and combinations thereof.

In illustrative embodiments, the at least one filler is present at arange of about 30-90 by weight percentage in the biocompatiblecomposition, while the one or more binders are present at a range ofabout 10-70 by weight percentage in the biocompatible composition.Likewise, the one or more additives are present at a range of about0.1-10 by weight percentage in the biocompatible composition in someembodiments, where the one or more solvents are present at a range ofabout 0.1-60 by weight percentage in the biocompatible composition insuitable embodiments. In some embodiments, the at least one indicatorregion is permanently affixed to the device. In other embodiments, thebiocompatible composition of the indicator is a material component ofthe device itself, e.g., the materials that constitute the device arecomposed of, inter alia, the biocompatible composition of the indicator.

In illustrative embodiments, the at least one indicator region ispermanently adhered to the device as one or more coated layers or as anindependently affixed layer by a surface application process selectedfrom coating, painting, encapsulation, dip coated, chemical adsorption,immobilization, piezoelectric printing, thermal printing, coatedrolling, roll-to-roll conveying, spray nozzle application, electroactivedeposition, chemical vapor deposition, magnetoactive deposition, laserinduction, and imprinting, and any combination thereof. In someembodiments, the biocompatible composition of the indicator is amaterial component of the device itself, e.g., the materials thatconstitute the device are composed of, inter alia, the biocompatiblecomposition of the indicator.

In illustrative embodiments, the at least one indicator region ispresent as a surface layer on the device, where the thickness of thesurface layer is about 100 μm to 3 mm. In certain embodiments, theirreversible identification is a visual and tactile identification. Insome embodiments, the modified state of the at least one indicatorregion renders the device clinically impractical for reuse. In certainembodiments the one or more superabsorbent polymers is sodiumpolyacrylate, where the sodium polyacrylate possesses a degree ofionization ranging from about 30-100 percent.

In one aspect, the present disclosure provides a method of manufacturinga single procedure device indicator, entailing (a) selecting a medicaldevice, (b) preparing the indicator, where the indicator is abiocompatible composition comprising at least one filler and one or morebinders that are present in the biocompatible composition at apredefined ratio by weight percentage, and (c) applying thebiocompatible composition to the medical device to form at least oneindicator region, where the at least one indicator region is configuredto transition from an unmodified state to a modified state in responseto an exposure. In illustrative embodiments the modified state of the atleast one indicator region irreversibly identifies that the medicaldevice has been subjected to the exposure after the single procedure.

In illustrative embodiments, the exposure entails contacting the medicaldevice including the at least one indicator region with water, where thewater contact occurs via one or more autoclave cycles, steamsterilization cycles, sterilization procedures, simple application ofwater and/or steam, aqueous disinfection, washing, and/or the sterileapplication of water or steam. In some embodiments, the exposure is oneor more autoclave steam sterilization cycles. In some embodiments, theexposure comprises subjecting the device including the at least oneindicator region to one or more steam sterilization cycles. In suitableembodiments, the one or more steam sterilization cycles are performedfor a duration at temperatures and pressures sufficient to (i)transition the at least indicator region from the unmodified state tothe modified state, and (ii) sterilize the device.

In some embodiments, the medical device is a single use orthopedicsurgical device. In some embodiments, the medical device is selectedfrom reamers, awls, rod benders, drill guides, guide tubes, distancegages, inserters, implant holders, clamps, portals, screwdrivers,spacers, distracters, plate benders, broaches, fusion plates, fusionscrews, spinal rods, spinal connectors, artificial discs,tissue-anchoring devices, fixation devices, Stineman pins, dilators,joint spreaders, rasps, fusion cages, Kerrisons and Rongeurs, andcombinations thereof. In certain embodiments, the biocompatiblecomposition further entails one or more solvents, additives,accelerants, surfactants, emulsifiers, reducing agents, fluidizingagents, detergents, wetting agents, and dispersants, and combinationsthereof.

In illustrative embodiments, the at least one filler is one or moresuperabsorbent polymers possessing a swelling capacity range of about30-500 fold the volume of the one or more superabsorbent polymers priorto being subjected to the exposure. In some embodiments, the one or moresuperabsorbent polymers is selected from polyacrylates, polyacrylamides,polyacrylamide copolymers, polyacrylic acid, sodium polyacrylate,potassium polyacrylate, lithium polyacrylate, ammonium polyacrylate,ethylene maleic anhydride copolymer, carboxymethylcellulose, polyvinylalcohol copolymers, polyethylene oxide, and copolymers ofpolyacrylonitrile, and combinations thereof. In some embodiments, theone or more binders are selected from alkyds, acrylics, vinyl-acrylics,polyurethanes, polyesters, melamine, epoxies, silanes, siloxanes, andoils, and combinations thereof.

In illustrative embodiments, the biocompatible composition furtherincludes a solvent selected from xylene, toluene, alcohols, and ketones,and combinations thereof. In some embodiments, the one or more additivesare selected from clays, kaolin, kaolinite, halloysite, diaspore,bentonite (Fuller's earth), ball clay, common clay, shale, fire clay,illite, chlorite, smectite minerals, quartz, limestone, silicatecompounds, and quartz, and combinations thereof, in certain embodiments.In suitable embodiments, the predefined ratio of the at least one filleris at a range of about 30-90 by weight percentage in the biocompatiblecomposition. In some embodiments, the predefined ratio of the one ormore binders are at a range of about 10-70 by weight percentage in thepresent in the biocompatible composition. In certain embodiments, theone or more additives are present at a range of about 0.1-10 by weightpercentage in the biocompatible composition.

In illustrative embodiments, the biocompatible composition of theindicator is prepared by mixing together the at least one filler and theone or more binders at the predefined ratios to produce a hydrogelslurry capable of transiting from the unmodified state to the modifiedstate in response to the exposure. In some embodiments, thebiocompatible composition further includes one or more solvents,additives, accelerants, surfactants, emulsifiers, reducing agents,fluidizing agents, detergents, wetting agents, and dispersants, andcombinations thereof. In some embodiments, the predefined ratio of theat least one filler is present at a range of about 30-90 by weightpercentage in the biocompatible composition, where the at least onefiller is one or more superabsorbent polymers possessing a swellingcapacity range of about 30-500 fold the volume of the one or moresuperabsorbent polymers prior to being subjected to the exposure. Inillustrative embodiments, the methods further entail adding to thehydrogel slurry one or more solvents, additives, accelerants,surfactants, emulsifiers, reducing agents, fluidizing agents,detergents, wetting agents, and dispersants, and combinations thereof.

In some embodiments, the one or more solvents are selected from one ormore of non-polar solvents, polar solvents, non-aqueous solvents,aqueous solvents, protic solvents, aprotic solvents, lipophilicsolvents, hydrophilic solvents, water-miscible solvents, andwater-immiscible solvents, and combinations thereof. In illustrativeembodiments, the one or more binders are dissolved in the one or moresolvents. In some embodiments, the one or more fillers, polymers and/orsuperabsorbent polymers (SAPs) are not miscible in the solvent. Insuitable embodiments, the one or more solvents are selected from xylene,toluene, alcohols, and ketones, and combinations thereof.

In illustrative embodiments, the modified state of the at least oneindicator region irreversibly identifies that the medical device hasbeen subjected to the exposure after the single procedure, and whereinthe exposure entails subjecting the medical device including the atleast one indicator region to water contact, where the contact withwater is selected from disinfection, washing, sterilizing, steamsterilization, and/or one or more autoclave cycles. In suitableembodiments, the medical device has a proximal end and a distal end, andwhere the at least one indicator region is positioned at or about theproximal end of the medical device. In suitable embodiments, theproximal end of the device and/or the indicator region is sufficientlylocated, configured, arranged and/or positioned on, or with respect to,the medical device such that the indicator region and/or proximal end ofthe device is not subjected to an exposure until after the singleprocedure.

In illustrative embodiments, the biocompatible composition is formulatedsuch that after the biocompatible composition is applied to a proximalend of a device, i.e., constituting the indicator region, thesuperabsorbent polymer (SAP) is sterically arrange throughout theindicator region to ensure that water, when present, is able tocontact—and accordingly swell—the SAP, i.e., the water is accessible tothe SAP for adsorption via SAP surface exposure. Likewise, in someembodiments of the present invention, the SAP molecules are contiguouslyconformed or are arranged in a substantially contiguous configurationwithin the biocompatible composition, and consequently throughout theindicator region, such that water, when present, is able to continuouslypercolate the indicator region until the SAP swelling capacity isachieved.

In some embodiments, the biocompatible composition of the indicator ispermanently adhered to the medical device as one or more coated layersor as an independently affixed layer by a surface application processselected from coating, painting, encapsulation, dip coated,immobilization, chemical adsorption, piezoelectric printing, thermalprinting, coated rolling, roll-to-roll conveying, spray nozzleapplication, electroactive deposition, chemical vapor deposition,magnetoactive deposition, laser induction, and imprinting, and anycombination thereof. In some embodiments, the biocompatible compositionof the indicator is a material component of the device itself, e.g., thematerials that constitute the device are composed of, inter alia, thebiocompatible composition of the indicator.

In illustrative embodiments, the biocompatible composition is applied tothe medical device by using a surface application process selected fromcoating, dip coating, encapsulating, chemical adsorption,immobilization, piezoelectric printing, thermal printing, coatedrolling, roll-to-roll conveying, spray nozzle application, electroactivedeposition, chemical vapor deposition, magnetoactive deposition, laserinduction, and imprinting, and any combination thereof. In illustrativeembodiments, the at least one indicator region is present as a surfacelayer on the medical device, and where the thickness of the surfacelayer is about 100 μm to 3 mm. The irreversible identification is avisual and tactile identification in certain embodiments. In someembodiments, the modified state of the at least one indicator regionrenders the device clinically impractical for reuse. In someembodiments, the one or more superabsorbent polymers is sodiumpolyacrylate. In some embodiments, the sodium polyacrylate possesses adegree of ionization ranging from about 30-100 percent.

In one aspect, the present disclosure relates to a single proceduredevice indicator, that include (a) a biocompatible compositioncomprising a superabsorbent polymer matrix, one or more binders, and oneor more additives that are present in the biocompatible composition atpredefined ratios by weight percentage in a mixture, solution and/orsolvent, and (b) a surgical device at least partially enveloped orencapsulated by the biocompatible composition thereby forming at leastone indicator region on the surgical device. The biocompatiblecomposition is further composed of, in some embodiments, one or moreaccelerants, surfactants, emulsifiers, reducing agents, fluidizingagents, detergents, wetting agents, and dispersants, and combinationsthereof.

In illustrative embodiments, the surgical device is a single useorthopedic surgical device. In some embodiments, the orthopedic surgicaldevice is selected from reamers, awls, rod benders, drill guides, guidetubes, distance gages, inserters, implant holders, clamps, portals,screwdrivers, spacers, distracters, plate benders, broaches, fusionplates, fusion screws, spinal rods, spinal connectors, artificial discs,tissue-anchoring devices, fixation devices, Stineman pins, dilators,joint spreaders, rasps, fusion cages, Kerrisons and Rongeurs, andcombinations thereof. In some embodiments, the surgical device possessesa proximal end and a distal end, where the at least one indicator regionis located at or about the proximal end of the surgical device.

In illustrative embodiments, the superabsorbent polymer matrix is ahydrogel polymer possessing a swelling capacity range of about 30-500fold the volume of the superabsorbent polymer matrix prior to beingsubjected to an exposure. In some embodiments, the hydrogel polymer isselected from polyacrylates, polyacrylamides, polyacrylamide copolymers,polyacrylic acid, sodium polyacrylate, potassium polyacrylate, lithiumpolyacrylate, ammonium polyacrylate, ethylene maleic anhydridecopolymer, carboxymethylcellulose, polyvinyl alcohol copolymers,polyethylene oxide, and copolymers of polyacrylonitrile, andcombinations thereof.

In suitable embodiments, the one or more binders are selected fromalkyds, acrylics, vinyl-acrylics, polyurethanes, polyesters, melamine,epoxies, silanes, siloxanes, and oils, and combinations thereof. In someembodiments, the solvent is selected from xylene, toluene, alcohols, andketones, and combinations thereof. In certain embodiments, the one ormore additives are selected from clays, kaolin, kaolinite, halloysite,diaspore, bentonite (Fuller's earth), ball clay, common clay, shale,fire clay, illite, chlorite, smectite minerals, quartz, limestone,silicate compounds, and quartz, and combinations thereof, in certainembodiments. In illustrative embodiments, the predefined ratio of thesuperabsorbent polymer matrix is at a range of about 30-90 by weightpercentage in the biocompatible composition. In illustrativeembodiments, the predefined ratio of the one or more binders is at arange of about 10-70 by weight percentage in the biocompatiblecomposition.

In suitable embodiments, the one or more additives are present at arange of about 0.1-10 by weight percentage in the biocompatiblecomposition. In some embodiments, the biocompatible composition of theat least one indicator region is permanently affixed to the surgicaldevice. In some embodiments, the at least one indicator region iscomposed of the biocompatible composition present as a surface layer onthe surgical device, where the thickness of the surface layer is about100 82 m to 3 mm. In some embodiments, the superabsorbent polymer matrixis a hydrogel formulation comprising sodium polyacrylate. Inillustrative embodiments, the sodium polyacrylate possesses a degree ofionization ranging from about 30-100 percent.

In some embodiments, the biocompatible composition is present atpredefined ratios by weight percentage in the mixture, solution and/orsolvent, where the mixtures, solutions and/or solvents are characterizedas non-polar, polar, non-aqueous, aqueous, protic, aprotic, lipophilic,hydrophilic, water-miscible, or water-immiscible, and/or combinationsthereof. In illustrative embodiments, the one or more binders aredissolved in the one or more mixtures, solutions and/or solvents. Insome embodiments, the one or more fillers, polymers and/orsuperabsorbent polymers (SAPs) are not miscible in the mixtures,solutions and/or solvents. In suitable embodiments, the one or moremixtures, solutions and/or solvents are selected from xylene, toluene,alcohols, and ketones, and combinations thereof.

In illustrative embodiments, the modified state of the at least oneindicator region irreversibly identifies that the medical device hasbeen subjected to the exposure after the single procedure, and whereinthe exposure entails subjecting the medical device including the atleast one indicator region to water contact, where the contact withwater is selected from disinfection, washing, sterilizing, steamsterilization, and/or one or more autoclave cycles. In suitableembodiments, the medical device has a proximal end and a distal end, andwhere the at least one indicator region is positioned at or about theproximal end of the medical device. In suitable embodiments, theproximal end of the device and/or the indicator region is sufficientlylocated, configured, arranged and/or positioned on, or with respect to,the medical device such that the indicator region and/or proximal end ofthe device is not subjected to an exposure until after the singleprocedure.

In illustrative embodiments, the biocompatible composition is formulatedsuch that after the biocompatible composition is applied to a proximalend of a device, i.e., constituting the indicator region, thesuperabsorbent polymer (SAP) is sterically arrange throughout theindicator region to ensure that water, when present, is able tocontact—and accordingly swell—the SAP, i.e., the water is accessible tothe SAP for adsorption via SAP surface exposure. Likewise, in someembodiments of the present invention, the SAP molecules are contiguouslyconformed or are arranged in a substantially contiguous configurationwithin the biocompatible composition, and consequently throughout theindicator region, such that water, when present, is able to continuouslypercolate the indicator region until the SAP swelling capacity isachieved.

The foregoing summary is illustrative only and is not intended to be inany way limiting. In addition to the illustrative aspects, embodiments,and features described above, further aspects, embodiments, and featureswill become apparent by reference to the following drawings and thedetailed description.

BRIEF DESCRIPTION OF THE FIGURES

FIGS. 1A-1B are illustrative representations concerning theintermolecular interactions, such as hydrogen bonding, between polymermatrix functional groups and water molecules. FIG. 1A shows hydrogenbonding between polymer matrix carboxylic acid groups and watermolecules. FIG. 1B depicts hydrogen bonding between the carboxylate iongroup groups of the polymer matrix and water molecules.

FIG. 2 is a schematic representation of a single-use superabsorbentpolymer indicator on a single procedure device prior to and followingsteam sterilization.

FIGS. 3A-3B are photographs of single-use superabsorbent polymerindicator pouches prior to and following steam sterilization. FIG. 3Ashows the indicator before being subjected to steam sterilization, whileFIG. 3B is a photograph of the indicators after steam sterilization.

FIGS. 4A-4B are photographs of single-use superabsorbent polymers coatedon the proximal end of a medical device prior to and following waterexposure. FIG. 4A shows the coated indicator before water exposure, andFIG. 4B is a photograph of the coated indicators after exposure towater.

DETAILED DESCRIPTION

In the following detailed description, reference is made to theaccompanying drawings, which form a part thereof. In the drawings,similar symbols typically identify similar components, unless contextdictates otherwise. The illustrative embodiments described in thedetailed description, drawings, and claims are not meant to be limiting.Other embodiments may be utilized, and other changes may be made,without departing from the spirit or scope of the subject matterpresented herein. It will be readily understood that the aspects of thepresent disclosure, as generally described herein, and illustrated inthe figures, can be arranged, substituted, combined, separated, anddesigned in a wide variety of different configurations, all of which areexplicitly contemplated herein.

As used herein, unless otherwise stated, the singular forms “a,” “an,”and “the” include plural reference. Thus, for example, a reference to“an indicator” can include a plurality of indicators.

As used herein, the term “about” will be understood by persons ofordinary skill in the art and will vary to some extent depending uponthe context in which it is used. If there are uses of the term which arenot clear to persons of ordinary skill in the art, given the context inwhich it is used, the term “about” in reference to quantitative valueswill mean up to plus or minus 10% of the enumerated value.

As used herein, the terms “amphipathic” or “amphiphilic” are meant torefer to any material that is capable of polar and non-polar, orhydrophobic and hydrophilic, interactions. These amphipathicinteractions can occur at the same time or in response to an externalstimuli at different times. For example, when a specific material orcoating, painting, encapsulation, and/or dip coating is said to be“amphipathic,” it is meant that such material or coating, painting,encapsulation, and/or dip coating can be hydrophobic or hydrophilicdepending upon external variables, such as, e.g., temperature, salinity,pH, etc.

The terms “assessing” and “evaluating” are used interchangeably to referto any form of measurement, and includes determining if an element ispresent or not. The terms “determining,” “measuring,” “assessing,” and“assaying” are used interchangeably and include both quantitative andqualitative determinations. Assessing may be relative or absolute.“Assessing the presence of” includes determining the amount of somethingpresent, as well as determining whether it is present or absent.

As used herein, the terms “binder” or “binders” refers to polymers ormaterials that facilitate adhesion, connection, coupling, binding,attachment, affixation, or joining of the biocompatible compositions ofthe indicators disclosed herein or the single-use indicators of thepresent disclosure to a substrate, e.g., a medical device. In someembodiments, the binders include, but are not limited to, alkyds,acrylics, vinyl-acrylics, polyurethanes, polyesters, melamine, epoxies,silanes, siloxanes, and oils, and combinations thereof. In someembodiments, the binder is dissolved in a solvent.

As used herein, the terms “biocompatible,” “biocompatible material,”“biocompatible polymer,” “indicator,” indicator materials,” “materials,”“polymer materials,” or “biocompatible indicators” refer to a syntheticor natural material that is, for example, non-toxic to biologicalsystems and/or congruent with biological processes. In this respect,biocompatibility of polymer materials denote minimal, negligible, or norisk of immunorejection, injury, damage and/or toxicity to living cells,tissues, organs, and/or biological systems. In illustrative embodiments,the biocompatible material is one or more superabsorbent polymersselected from, but not limited to, polyacrylates, polyacrylamides,polyacrylamide copolymers, polyacrylic acid, sodium polyacrylate,potassium polyacrylate, lithium polyacrylate, ammonium polyacrylate,ethylene maleic anhydride copolymer, carboxymethylcellulose, polyvinylalcohol copolymers, polyethylene oxide, and copolymers ofpolyacrylonitrile, polylactic acid, polyglycolic acid,poly(lactide-co-glycolide), and/or poly(L-lactide), and the like, andcombinations thereof.

As used herein, the term “composition” refers to a product withspecified ingredients in the specified amounts, as well as any productwhich results, directly or indirectly, from combination of the specifiedingredients in the specified amounts.

As used herein, the terms “device” or “instrument” refer to a substrateof which an indicator is applied to or affixed, where the indictor isrepresentative of whether the device or instrument has been discharged.Typically, the devices and instruments of the present disclosure relateto single procedure medical devices and instruments, but are notnecessarily limited thereto. In suitable embodiments, the medical devicehas a proximal end and a distal end, and where the at least oneindicator region is positioned at or about the proximal end of themedical device. In suitable embodiments, the proximal end of the deviceand/or the indicator region is sufficiently located, configured,arranged and/or positioned on, or with respect to, the medical devicesuch that the indicator region and/or proximal end of the device is notsubjected to an exposure until after the single procedure.

In this respect, and in other words, the medical devices and instrumentsof the present disclosure include a proximal end and a distal end, wheretypically, for example, the distal end of the device or instrument isthe functional region that, in illustrative embodiments, contacts thearea of the patient being operated on, e.g., the distal end is typicallynot the device region contacted by the clinician or surgeon. Theproximal end, on the other hand, for example, is the structural regionthat, in illustrative embodiments, is contacted by the clinician orsurgeon. In other words, the proximal end or region of a medical devicetypically does not come into contact with a patient's bodily fluids,e.g., blood. In illustrative embodiments, the proximal end of the deviceis the region that, at least in part, is composed of or harbors thesingle-use indicators disclosed herein.

In some embodiments, the single procedure medical device is a single useorthopedic surgical device. In illustrative embodiments, the medicaldevice or instrument is selected from, but not limited to, single-usereamers, awls, rod benders, drill guides, guide tubes, distance gages,inserters, implant holders, clamps, portals, screwdrivers, spacers,distracters, plate benders, broaches, fusion plates, fusion screws,spinal rods, spinal connectors, artificial discs, tissue-anchoringdevices, fixation devices, Stineman pins, dilators, joint spreaders,rasps, fusion cages, Kerrisons and Rongeurs, and combinations thereof.

As used herein, the term “discharge status” of a single procedure deviceor instrument refers to the lifecycle status of the device orinstrument. In suitable embodiments, for example, a device or instrumentthat has been “affirmatively discharged,” as used herein, is anindication that the status of the device or instrument is an“end-of-use” status, i.e., the device should not be redeployed for asecond or repeat procedure.

As used herein, the term “encapsulation” or “encapsulating” refers tothe retention of substance within a compartment, delineated by aphysical barrier. For example, the encapsulated agents described hereinrefer to agents which are retained within, and surrounded by a physicalbarrier, such as a capsule or nanocapsule. The term, “nanocapsule,” asused herein, moreover, refers to a particle having a hollow core that issurrounded by a shell, such that the particle has a size of less thanabout 1,000 nanometers. When a nanocapsule includes an agent, the agentis typically located in the core that is surrounded by the shell of thenanocapsule.

As used herein, the term “exposure” refers to circumstances where amedical device, instrument, apparatus, biocompatible composition,indicator, indicator region, and/or an unmodified indicator region,alone or collectively, are subjected to one or more conditions,applications, and/or the presence of water, steam, sterilization, anautoclave cycle, aqueous disinfection or washing, the sterileapplication of water or steam, or other conditions where the medicaldevice, instrument, apparatus, biocompatible compositions, indicator,indicator region, and/or the unmodified indicator region, alone orcollectively, come into contact with water.

Along these lines, the biocompatible compositions of the presentdisclosure are formulated such that after a biocompatible composition isapplied to a proximal end of a device, i.e., constituting the indicatorregion, the superabsorbent polymer (SAP) is sterically arrangethroughout the indicator region to ensure that water, when present, isable to contact—and accordingly swell—the SAP, i.e., the water isaccessible to the SAP for adsorption via SAP surface exposure. Likewise,in some embodiments of the present invention, the SAP molecules arecontiguously conformed or are arranged in a substantially contiguousconfiguration within the biocompatible composition, and consequentlythroughout the indicator region, such that water, when present, is ableto continuously percolate the indicator region until the SAP swellingcapacity is achieved.

As used herein, the terms “hydrogel,” “hydrogel matrix,” “polymermatrix,” or “matrix” are interchangeably used, and encompass polymer andnon-polymer based matrices. Hydrogels, in this regard, as used herein,are typically continuous networks of hydrophilic polymers that absorbwater. “Matrix” is also meant to refer to all other matrix or hydrogelcompositions disclosed herein, including compositions that containpolymers, copolymers, terpolymer, and complexed polymer matrices, i.e.,matrices that contain one, two, three, four or more monomeric ormultimeric constituent units. The terms “hydrogel polymers” or “matrixpolymer materials” refer to the materials used to make the matrices orhydrogels of the present disclosure. Such terms refer to both monomericunits of the materials and the polymers or co-polymers made therefrom.

As used herein, the term “polymer” refers to a macromolecule made ofrepeating monomer or multimer units. Polymers of the present disclosureare polymeric forms of, and include, but are not limited to,polyacrylates, polyacrylamides, polyacrylamide copolymers, polyacrylicacid, sodium polyacrylate, potassium polyacrylate, lithium polyacrylate,ammonium polyacrylate, ethylene maleic anhydride copolymer,carboxymethylcellulose, polyvinyl alcohol copolymers, polyethyleneoxide, and copolymers of polyacrylonitrile, polylactic acid,polyglycolic acid, poly(lactide-co-glycolide), poly(L-lactide),poly(hyaluronic acid), poly(sodium alginate), poly(ethylene glycol),poly(lactic acid) polymers, poly(glycolic acid) polymers,poly(lactide-co-glycolides), poly(urethanes), poly(siloxanes) orsilicones, poly(ethylene), poly(vinyl pyrrolidone), poly(2-hydroxy ethylmethacrylate), poly(N-vinyl pyrrolidone), poly(methyl methacrylate),poly(acrylic acid), poly(vinyl acetate), polyacrylamide,poly(ethylene-co-vinyl acetate), poly(methacrylic acid), polylacticacid, poly(L-lactide) (PLLA), polyglycolic acids, nylons, polyamides,polyanhydrides, poly(ethylene-co-vinyl alcohol, polycaprolactone,polyvinylhydroxide, poly(ethylene oxide), and polyorthoesters or aco-polymer or terpolymer formed from at least two or three members ofthe groups, respectively.

Along the same lines, the terms “superabsorbent polymer,” “SAP,” or“water-absorbing polymer,” are interchangeably referred to herein, andencompass solutions or powders that possess the ability to absorb andretain large amounts of a liquid, e.g., water, relative to their ownmass. In part, the properties of such water-absorbing polymers, whichmay be classified as hydrogels when cross-linked, can be attributed tothe intermolecular interactions, e.g., hydrogen bonding, between thepolymer material and water molecules. Depending on the ionic strength ofany particular aqueous solution, SAP's as disclosed herein possess aswelling capacity, e.g., the ability to absorb one or more fluids, e.g.,water, range of about 30-700 fold its weight in water compared to theweight or volume of the SAP as dry particulate matter, in a desiccatedstate, unsaturated state, or prior to being subjected to an exposure, asdefined herein, water, and/or a sterilization cycle, and combinationsthereof.

As used herein, “prevention” or “preventing” of an infection orcondition refers to a method or indicator that, in a statistical sample,reduces the occurrence of the infection or condition in a sample patientpopulation relative to an control sample patient population. As usedherein, preventing an infection or condition includes the prevention ofheath care associated infections, i.e., nosocomial infections, bypreventing a second or subsequent use of a single procedure medicaldevice or instrument.

As used herein, the term “solvent” refers to a liquid in which a soluteis dissolved to form a solution. As disclosed herein, the polymers,superabsorbent polymers (SAPs), hydrogels and the like, typically arenot miscible in a solvent, whereas the one or more binders as disclosedherein typically are miscible in a solvent as used herein. In someembodiments, one or more solvents are selected from one or more ofnon-polar solvents, polar solvents, non-aqueous solvents, aqueoussolvents, protic solvents, aprotic solvents, lipophilic solvents,hydrophilic solvents, water-miscible solvents, and water-immisciblesolvents, and combinations thereof. In illustrative embodiments, the oneor more solvents are selected from xylene, toluene, alcohols, andketones, and combinations thereof. As disclosed herein, although theterm solvent typically refers to a liquid solution, the term “solution”does not necessarily invoke the term “solvent” as used herein. Likewise,the terms “slurry” and “mixture” are separate and distinct from a“solvent” as used herein.

As used herein, the terms “substantial” or “substantially” within thecontext of a “substantially enveloped” surface or region or a“substantially aligned” configuration, refer to, e.g., total or completeenvelopment, encapsulation or alignment, and the like, but also includeslesser than complete or total envelopment, encapsulation or alignment,and the like, insofar as the intended purpose for performing the act canbe carried out to the same extent as if the, e.g., envelopment,encapsulation or alignment, were total or complete. Likewise, in someembodiments of the present invention, the SAP molecules are contiguouslyconformed or are arranged in a “substantially contiguous configuration”within the biocompatible composition, and consequently throughout theindicator region, such that water, when present, is able to continuouslypercolate the indicator region until the SAP swelling capacity isachieved.

As used herein, the term “wettability” or “wetting” refers to theability of a substance to maintain surface contact with a differentsubstance or surface. Surface contact results from intermolecularinteractions between a substance and the contacted surface. Wetting, andthe surface forces that control wetting, are also responsible for otherrelated effects, including capillary action or capillary effects. Forexample, when an indicator adheres to a surface of a device thewettability, or degree of wetting, can be calculated in terms of theforce balance between the adhesive and cohesive forces. Wettability canbe altered by, for example, adding different combinations andconcentrations of materials to, for example, a biocompatiblecomposition.

Single Procedure Indicators

When considering the potential for single procedure medical devices tobecome erroneously reintroduced into a surgical setting, i.e., after itsinitial—and presumptive only intended—use, the consequences can besevere. Whether intentional or otherwise, recirculation of singleprocedure devices precipitates a non-negligible health care expense bothfrom a patient's well-being and an economic standpoint. See, e.g.,Schultz, J. B., “Disposables in the O.R. ‘Cover Story: Disposables, ECAMedical Instruments,’” (2013). Indeed, the impetus behind the advent ofsingle-use medical instruments emanates directly from a desire toeliminate nosocomial infections. As single procedure devices becamecommonplace in the health care setting, various processes have beenimplemented to mitigate reprocessing and nosocomial pathogenesis.

Single procedure instruments, in this regard, provide a measure ofmitigation with respect to persistent clinical concerns, e.g., acquirednosocomial infections, and economic costs, e.g., patient treatment andthe associated increase in frequency and duration of hospital visits.The advantages of employing single-procedure instruments are notdifficult to appreciate. Along these lines, some of the benefitsattendant to using single procedure medical devices include, but are notlimited to (i) decreased thermal necrosis of bone inasmuch as sharp,precise and accurate, surgical tools do not produce the same frictionalconsequences and osteological debris associated with the use of dullinstruments, (ii) reduced surgical site contamination and accompanyinginfections, (iii) more efficient hospital inventory management insofaras the inventory burden is lessened with off-the-shelf kits for implantsand related procedures, (iv) improved patient safety and clinicianconfidence, and (v) the elimination of substantial life-cycle supportcosts and associated carbon footprint encumbrances, e.g., cleaning,handling and re-sterilization of reusable medical devices.

There remains a need, however, for readily ascertainable indicationsthat conspicuously identify when single procedure instruments are attheir end-of-use. Such indicators would markedly decrease thepossibility of health care related infections associated with theunintentional reuse of single procedure devices. Nosocomial infectionsand surgical errors are coterminous with respect to the use of recycledsingle procedure devices, i.e., at least to the extent that post processdisinfection and sterilization is typically not extensive, while thecause of field failure concerning single-use devices similarly stemsfrom second or repeated procedures with devices that may only becalibrated for a single procedure. As such, the import of addressing theforegoing issues by having a very distinct indication that a singleprocedure device has been discharged is readily apparent, where ensuringthat such devices are not placed back in the operating room is alingering health care dilemma.

Following a surgical operation, as noted above, end-of-use singleprocedure devices typically undergo one or more disinfection and/orsterilization cycles before they are ultimately discarded. In manyinstances, such sterilization cycles are performed via an autoclave,where, in the presence of elevated temperatures and pressures, waterbecomes superheated steam that consequently functions to sterilize theenclosed contents of the autoclave. Likewise, disinfection of singleprocedure devices, or simple washing, may also occur prior to, after, orto the exclusion of a steam sterilization cycle. Similar to steamsterilization, in this respect, such disinfection or washing alsosubjects the single procedure device to the presence of water. An aspectof the present invention takes advantage of these processes bydeveloping water-sensitive, steam-sensitive, water-absorbing, materialsthat serve as single-use indicators when applied or connected to anydevice or instrument that will be or has been subjected to the waterand/or steam sterilization.

In illustrative embodiments, the single use indicators of the presentinvention operate in a distinct and irreversible manner as furtherdetailed herein. Some embodiments of the present invention relate toindicator materials that are one or more superabsorbent polymerspossessing a swelling capacity range of about 30-700 fold the volume ofthe superabsorbent prior to being subjected to a steam sterilizationcycle. One non-limiting example of a superabsorbent polymer of thepresent invention is sodium polyacrylate. Ionized forms of sodiumpolyacrylate, and related materials with similar properties as furtherdetailed herein, experience a substantial increase in volume andmorphological changes when subjected to water, e.g., steamsterilization. Such distinct indications impart both a visual andtactile modification thereby providing health-care personnel withreadily ascertainable indications that the device has been steamsterilized, and accordingly is at its end-of-use.

To the extent that other indicator techniques have been previouslydisclosed, see e.g., U.S. Pat. No. 8,567,338, disclosing reprocessingindicators for single patient use medical instruments, and U.S. Pat. No.8,157,747, describing single-use indicators for surgical instruments,those and related systems concern reversible colorimetric indicatorsthat fail to provide an irreversible visual and tactile change ormodification associated with sterilization processes. Equally asimportant with respect to the present single-use indicators is themechanism underlying the indicator modification, which elicits avolumetric and morphological modification that is not dependent upon auser's ability to ascertain reversible color changes that may be lessthan apparent.

Along these lines, superabsorbent materials, such as, for example,water-absorbing polymers, are macromolecules composed of one or morehydrophilic backbones. These polymers typically contain carboxylic acidfunctional groups, and salts or esters thereof, which, depending ontheir ionization state in solution, may be present as the conjugate baseof carboxylic acid moieties, i.e., carboxylate ions. These functionalgroups impart the hydrophilic nature of such polymers via hydrogenbonding interactions that occur between the electronegative oxygen atomsand electron deficient hydrogen atoms when in an aqueous solution. SeeFIG. 1. The polymer matrices of the present invention are consideredsuperabsorbent polymers, in illustrative embodiments, due to the factthat either conjugate form, i.e., the carboxylic acid and carboxylateion groups, of the polymers electrostatically bond with water molecules.See FIG. 1A and FIG. 1B. In concert with decreasing the energy of asystem, these intramolecular interactions function to disperse thepolymers of the present invention in an aqueous solution, which resultsin an increase in system entropy.

The polymer chains of the present indicators, in illustrativeembodiment, form a three dimensional lattice via cross-linking. Thisnetwork structure matrix therefore not only increases in volume bypermitting matrix hydration, but also remains in the hydrated stateinasmuch as the cross-linked polymers prevent the dissemination of watermolecules. Put simply, when the water-absorbing polymers, as disclosedherein, are present as, for example, a sodium salt of the carboxylicacid conjugate base, this sodium carboxylate in solution produces asosmotic imbalance. These hydrated sodium ions, albeit fluid in solution,cannot disperse from the gel lattice, which consequently imparts anirreversible indicator as described herein. The enhanced hydrophilicityof the polymer matrix indicators of the present invention, i.e., theirability to absorb and retain water, is referred to as the material'sswelling capacity.

In some embodiments, the swelling capacity range of the one or morepolymers, superabsorbent polymers, polymer matrices, hydrogels and/orindicator materials of the present invention is from about 10, 50, 100,200, 300, 400 or 500-fold to from about 300, 400, 500, 600, 700, 800,900 or 1000-fold the weight or volume of the one or more superabsorbentpolymers, polymer matrices, polymers, hydrogels and/or indicatormaterials of the present invention prior to being hydrated per anexposure. In illustrative embodiments, the swelling capacity range ofthe one or more polymers, superabsorbent polymers, polymer matrices,hydrogels and/or indicator materials of the present invention is fromabout 300, 400 or 500-fold to from about 600, 700 or 800-fold the weightor volume of the one or more superabsorbent polymers, polymer matrices,polymers, hydrogels and/or indicator materials of the present inventionprior to being hydrated per an exposure.

In this regard, the biocompatible compositions of the present disclosureare formulated such that after the biocompatible composition is appliedto a proximal end of a device, i.e., constituting the indicator region,the superabsorbent polymer (SAP) is sterically arrange throughout theindicator region to ensure that water, when present, is able tocontact—and accordingly swell—the SAP, i.e., the water is accessible tothe SAP for adsorption via SAP surface exposure. Likewise, in someembodiments of the present invention, the SAP molecules are contiguouslyconformed or are arranged in a substantially contiguous configurationwithin the biocompatible composition, and consequently throughout theindicator region, such that water, when present, is able to continuouslypercolate the indicator region until the SAP swelling capacity isachieved.

In some embodiments, the hydration of the one or more polymers,superabsorbent polymers, polymer matrices, hydrogels and/or indicatormaterials of the present invention is through an exposure. In suitableembodiments, the exposure is an exposure to water, e.g., via steamsterilization, or super-heated steam. In some embodiments, the water,steam and/or super-heated steam exposure occurs in an autoclave. Incertain embodiments, one or more autoclave cycles are used as theexposure. Steam autoclave exposures can be performed using one or moreof a gravity cycle, pre-vacuum cycle, steam flush pressure pulse cycle,and post-vacuum cycles. It will be readily apparent to one skilled inthe art that the foregoing and various other steam sterilization cycles,as well as other aqueous sterilization procedures, can be implementedwith respect to the present invention insofar as such cycles entail therequisite moisture, temperature, and/or pressures required to transitionthe indicators, in some embodiments, from an unmodified state to amodified state.

In some embodiments of the present invention, the exposure is one ormore autoclave gravity cycles, pre-vacuum cycles, steam flush pressurepulse cycles, and post-vacuum cycles. In illustrative embodiments, theexposure is one or more autoclave gravity cycles. A non-limiting exampleof an autoclave gravity cycle steam sterilization procedure entailstemperatures ranging from about 200, 300 or 400° F. or ° C. to fromabout 300, 400 or 500° F. or ° C. In some embodiments, the autoclavecycle is performed at about 274° F. The duration of an autoclave cycle,in suitable embodiments, ranges from about 5, 10, 15, 20, 25 or 30minutes (min) or hours (h) to about from 15, 20, 25, 30, 40 or 50minutes (min) or hours (h). In some embodiments, the duration of anautoclave cycle is about 18-20 minutes followed by an equal amount oftime in a drying cycle.

It will be readily apparent to the skilled artisan that numerousadditional variables can impact the rate and extent of indicatormodification, polymerization, swelling, solidification, and/orcongealing, etc. Such factors include, for example, percent humidity orhydration, CO₂ concentration, and/or temperature, etc., associated withan autoclave cycle. The skilled artisan will readily appreciate thatappropriate adjustments can optimize indicator volume, size, weight,morphology, consistency, viscosity and overall indication appearance andtexture for specific or desired uses.

In one aspect, the present disclosure relates to a single-use deviceindicator that includes a biocompatible composition composed of one ormore of a filler, polymer, matrix, hydrogel, indicator materials, and/ora superabsorbent polymer matrix. The composition is “biocompatible,” tothe extent that the foregoing materials are low- or non-toxic tobiological systems and/or congruent with biological processes. In thisrespect, biocompatibility of the materials present minimal or no risk ofimmunoreactivity, injury, damage and/or toxicity to living cells,tissues, organs, and/or biological systems.

In illustrative embodiments, the one or more fillers, polymers,matrices, hydrogels, indicator materials, and/or superabsorbent polymermatrices are, for example, but not limited to, monomers, copolymers,terpolymers and/or polymers, and salts, esters, and ionized conjugates,of one or more of polyacrylates, polyacrylamides, polyacrylamidecopolymers, polyacrylic acid, sodium polyacrylate, potassiumpolyacrylate, lithium polyacrylate, ammonium polyacrylate, ethylenemaleic anhydride copolymer, carboxymethylcellulose, polyvinyl alcoholcopolymers, polyethylene oxide, polyacrylonitrile, polylactic acid,polyglycolic acid, poly(lactide-co-glycolide), poly(L-lactide), siliconeacrylate, acrylate with enhanced hydrophilic surface functionality,siloxane acrylate, hexafocon A, enflufocon A, enflufocon B, hioxifilconB, hioxifilcon D, hioxifilcon A, polymacon, methafilcon A,2-hydroxyethyl methacrylate (2-HEMA), 2,3-dihydrosypropryl methacrylate(Glycerol Methacrylate, GMA), polymethyl methacrylate (PMMA),acrylamide, poly(hyaluronic acid), poly(sodium alginate), poly(ethyleneglycol) (PEG), poly(lactic acid) polymers, poly(glycolic acid) polymers,poly(lactide-co-glycolides) (PLGA), poly(urethanes), poly(siloxanes)silicones, poly(ethylene), poly(vinyl pyrrolidone), poly(2-hydroxy ethylmethacrylate), poly(N-vinyl pyrrolidone), poly(methyl methacrylate),poly(vinyl alcohol) (PVA), poly(acrylic acid), poly(vinyl acetate),polyacrylamide, poly(ethylene-co-vinyl acetate), poly(methacrylic acid),polylactic acid (PLA), poly(L-lactide) (PLLA), polyglycolic acids (PGA),polyamides, polyanhydrides, poly(ethylene-co-vinyl alcohol) (EVOH),polycaprolactone, polyvinylhydroxide, poly(ethylene oxide) (PEO),polyorthoesters, poly(N-isopropylacrylamide) (PIPAAm),N,N-dimethylaminopropyl acrylamide (DMAPAAm),poly(N-acryloylpiperidine)-cysteamine (pAP), PIPAAM-carboxymethyldextran benzylamide sulfonate/sulfate (PIPAAm-CMDBS),N,N-methylene-bis-acrylamide cross-linked polymer, PIPAAm-PEGN-isopropylacrylamide, N,N-dimethylacrylamide,2-hydroxyethylmethacrylate, N-hydroxyethyl acrylamide,N-vinyl-2-pyrrolidone, 4-pentenoic acid, N-isopropyl methacrylamide,N-methoxymethyl-N- isopropylacrylamide,2-(dimethylmaleimido)-N-ethylacrylamide, N,N-methylene-bis-acrylamideand PIPAAm-PEG, and combinations thereof including cross-linkedpolymers, co-polymers and/or terpolymers thereof, and combinationsthereof.

Examples of acceptable salts include, but are not limited to, cationicsalts, such as, but not limited to, sodium, potassium, lithium, calcium,magnesium, ammonium and alkylammonium; sulfates, phosphates, mesylates,bismesylates, tosylates, lactates, tartrates, malates, bis-acetates,citrates, bishydrochloride salts, acid addition salts of inorganic acidssuch as hydrochloric, orthophosphoric, sulfuric, phosphoric, nitric,carbonic, boric, sulfamic and hydrobromic acids; or salts of organicacids such as acetic, propionic, butyric, tartaric, maleic,hydroxymaleic, fumaric, citric, lactic, mucic, gluconic, benzoic,succinic, oxalic, phenylacetic, methanesulfonic, trihalomethanesulfonic,toluenesulfonic, benzenesulfonic, isethionic, salicylic, sulphanilic,aspartic, glutamic, edetic, stearic, palmitic, oleic, lauric,pantothenic, tannic, ascorbic, valeric and orotic acids. Salts of aminegroups may also comprise quaternary ammonium salts in which the aminonitrogen atom carries a suitable organic group such as an alkyl,alkenyl, alkynyl or aralkyl moiety. The salts may be formed byconventional means, such as by reacting the free base form of thecompound with one or more equivalents of the appropriate acid in asolvent or medium in which the salt is insoluble, or in a solvent suchas water which is removed in vacuo or by freeze drying or by exchangingthe anions of an existing salt for another anion on a suitable ionexchange resin.

In illustrative embodiments, the one or more fillers, polymers,matrices, hydrogels, indicator materials, and/or superabsorbent polymermatrices are polyacrylic acid and/or sodium polyacrylate. While suchbiocompatible compositions are employed with respect to the presenttechnology, in suitable embodiments, substantially similar compositionsmay be used in certain embodiments. Such substantially similarcompositions include, but are not limited to, e.g., related molecules,materials, compounds, polymers, and compositions possessing a similar oridentical functional and/or structural profile or are coterminous withthe physical propertied of the compositions used herein. With respect tothe biocompatible composition properties, characteristics or parameters,which allow for a substantially similar or identical indicator matricesto precipitate, these compositions are also acceptable in suitableembodiments. Likewise, the present disclosure contemplates one or morestructures, conjugates, compounds, compositions and the like, consistentwith the absorbance profile, swelling capacity, molecular and/or stericprofiles, conformation, structural and/or empirical formulations,stoichiometric ratios, spectrophotometric profiles, NMR profiles,refractive indices, liquid transition temperatures, and/or other dataprofiles consistent with the present compositions.

The biocompatible composition of the single-use device indicators of thepresent disclosure also include one or more binders and/or one or moreadditives that are present in the biocompatible composition atpredefined ratios by weight percentage in a solvent or solution atpredefined ratios by weight percentage with respect to the biocompatiblecomposition. The binders, for example, include, but are not limited to,alkyds, acrylics, vinyl-acrylics, polyurethanes, polyesters, melamine,epoxies, silanes, siloxanes, and oils, and combinations thereof.Non-limited examples of suitable epoxies in this respect includenon-aromatic based epoxy resins, aliphatic epoxy resins, alicyclic epoxyresins, TGIC, epoxy resins with rings containing nitrogen such as ahydantoin epoxy resin, a hydrogenated epoxy resin, aliphatic epoxyresins, glycidyl ether type epoxy resins, dicyclo-type epoxy resins, anda naphthalene type epoxy resins, and combinations thereof.

The binders in this regard function to secure the polymer indicators ofthe present invention to the single procedure device or to encapsulatethe device, where, in some embodiments, the binder and/or biocompatiblecomposition of the indicator is a material component of the deviceitself, i.e., it is coterminous with the structure of the device. Thebinders of the present invention facilitate the attachment of thebiocompatible indicator composition to the single procedure device inillustrative embodiments. In some embodiments, the at least oneindicator region is permanently affixed to the device. In otherembodiments, the biocompatible composition of the indicator is amaterial component of the device itself, e.g., the materials thatconstitute the device are composed of, inter alia, the biocompatiblecomposition of the indicator.

In illustrative embodiments, the biocompatible composition of theindicator is permanently adhered to the medical device as one or morecoated layers or as an independently affixed layer by a surfaceapplication process selected from coating, painting, encapsulation, dipcoating, spray drying, chemical adsorption, piezoelectric printing,thermal printing, coated rolling, roll-to-roll conveying, spray nozzleapplication, electroactive deposition, chemical vapor deposition,magnetoactive deposition, laser induction, imprinting, deposition, andimmobilizing, and any combination thereof. As used herein, the term“immobilizing” refers to the ability to retain the biocompatiblecomposition of the indicator in or on a device surface, component,region or matrix. In some embodiments, immobilization also refers to,but is not limited to, adsorption, covalent binding, entrapment,membrane confinement, and cross-linking.

Additionally or alternatively, the indicator compositions of interestcan be conjugated to a solid support, such as a bead or other material,which is subsequently affixed to the devices and instruments of thepresent invention or is a component material of such apparatuses. Inaddition, a first solid support such as a bead can also be conjugated,if desired, to a second solid support, which can be a second bead, thedevice or instrument, and/or other support structures, by any suitablemeans, including those disclosed herein for conjugation of a polymer orother material to support, device and/or instruments as disclosedherein. In some embodiments, the at least one indicator region ispermanently affixed to the device. While in other embodiments, thebiocompatible composition of the indicator is a material component ofthe device itself, e.g., the materials that constitute the device arecomposed of, inter alia, the biocompatible composition of the indicator.

The devices of the present invention, moreover, have a proximal end anda distal end, where the at least one indicator region is positioned ator about the proximal end of the medical device. In suitableembodiments, the proximal end of the device and/or the indicator regionis sufficiently located, configured, arranged and/or positioned on, orwith respect to, the medical device such that the indicator regionand/or proximal end of the device is not subjected to an exposure untilafter the single procedure.

Certain embodiments of the present invention include depositiontechniques, such as, e.g., piezoelectric ink-jet processes (see, e.g.,U.S. Pat. Nos. 7,051,654 and 5,668,581 and U.S. Pat. Pub. No.2010/0033545), including single or multiplex configurations (see, e.g.,U.S. Pat. No. 6,997,550), liquid nozzle spray (see, e.g., U.S. Pat. Pub.No. 2009/0087896), electroactive deposition processes (see, e.g., U.S.Pat. Pub. No. 2002/0008746), magnetoactive deposition processes,laser-induced forward transfer processes, laser printing utilizingnano-laser and femto-laser technologies and/or polydimethylsiloxane(PDMS) stamp for microcontact printing. All of the foregoing patents andpatent publications are hereby incorporated by reference in theirentirety.

Solvents and solutions used in some embodiments of the present inventionare typically inert insofar as the solvent or solution do not manifestphysical, biological and/or chemical properties that would bedeleterious to the intended use and/or purpose of the present invention.In suitable embodiments, the biocompatible composition is present atpredefined ratios by weight percentage in a mixture, solution and/orsolvent, where the mixtures, solutions and/or solvents are characterizedas non-polar, polar, non-aqueous, aqueous, protic, aprotic, lipophilic,hydrophilic, water-miscible, or water-immiscible, and/or combinationsthereof. In illustrative embodiments, the one or more binders aredissolved in the one or more mixtures, solutions and/or solvents. Insome embodiments, the one or more fillers, polymers and/orsuperabsorbent polymers (SAPs) are not miscible in the mixtures,solutions and/or solvents. In suitable embodiments, the one or moremixtures, solutions and/or solvents are selected from xylene, toluene,alcohols, and ketones, and combinations thereof.

In particular, with respect to the solvents of the present invention, insome embodiments, the solvent is selected from xylene, toluene,alcohols, and ketones, and combinations thereof. In certain embodiments,a solvent is not used to form the biocompatible compositions of theindicator. In some embodiments, one or more solvents are used to formthe biocompatible compositions of the indicator. In this respect,illustrative embodiments of the present invention include one or morebinders dissolved in a solvent.

The above-mentioned biocompatible compositions, fillers, binders,solvents, polymers, matrices, hydrogels, indicator materials, and/orsuperabsorbent polymer matrices may further contain an appropriateadditive depending on purposes and efficacy of the additive to theoverall functionality of the indicator. Examples of the above-mentionedadditives include, but are not limited to, one or more second oradditional fillers, binders, and solvents, while such additives may alsoinclude, for example, accelerants, surfactants, emulsifiers, reducingagents, fluidizing agents, detergents, wetting agents, dispersants,diluents, antioxidants, denaturants, dyes, pigments, discolorationinhibitors, UV absorbers, softening agents, stabilizers, plasticizers,antifoaming agents, reinforcing agents, hardening agents,hardening-accelerator agents, binding conjugates, curing agents and/orother constituents, and combinations thereof. In certain embodiments,the one or more additives are not used to form the biocompatiblecompositions of the indicator. In other embodiments, one or moreadditives are used to form the biocompatible compositions of theindicator.

Viscosity agents include, but are not limited to, methylcellulose,polyvinyl alcohol, starch, and combinations or mixtures thereof. Thekind, number, and amount of additives contained in a composition, andmore specifically in a biocompatible composition, may be appropriatelyset depending on purposes. Exemplary additives of the present disclosureinclude, but are not limited to, one or more clays, kaolin, kaolinite,halloysite, diaspore, bentonite (Fuller's earth), ball clay, commonclay, shale, fire clay, illite, chlorite, smectite minerals, quartz,limestone, silicate compounds, and quartz, and combinations thereof, incertain embodiments. In certain embodiments, the one or more additivesare not used to form the biocompatible compositions of the indicator. Inother embodiments, one or more additives are used to form thebiocompatible compositions of the indicator.

In illustrative embodiments, one or more of the at least one filler, oneor more binders, one or more additives, and the solvent, alone,collectively, and in various combinations, are combined to form amixture at predefined ratios. These particular predefined ratios orconcentrations that provide for the biocompatible composition of theindicator material to function in accord with its intended use as anirreversible indicator of water exposure and/or steamsterilization—which is coterminous with an end-of-use discharge statusfor such devices—while also possessing characteristics that allow forsuch compositions to at least partially envelope, encapsulate, contact,integrate, intercalate, bind, affix, adhere and/or couple, and the like,to a surgical device thereby forming at least one indicator region asdetailed herein.

In certain embodiments, the one or more fillers, polymers, matrices,hydrogels, indicator materials, and/or superabsorbent polymer matricesare present at a predefined ratio in the biocompatible composition at arange of about 0.001, 0.01, 0.1, 1, 5, 10, 20, 30 or 40% by dry weightpercentage or (w/v) to from about 40, 50, 60, 70, 80, 90, 95 or 99% bydry weight percentage or (w/v). In some embodiments, the one or morefillers, polymers, matrices, hydrogels, indicator materials, and/orsuperabsorbent polymer matrices are present at a predefined ratio in thebiocompatible composition at a range of about 30% by dry weightpercentage or (w/v) to from about 90% by dry weight percentage or (w/v).

Illustrative embodiments of the present invention, for example, entail apredefined ratio of the one or more binders in the biocompatiblecomposition at a range of about 0.001, 0.01, 0.1, 1, 5, 10, 20, 30 or40% by dry weight percentage or (w/v) to from about 40, 50, 60, 70, 80,90, 95 or 99% by dry weight percentage or (w/v). In some embodiments,the one or more binders are present at a predefined ratio in thebiocompatible composition at a range of about 10% by dry weightpercentage or (w/v) to from about 70% by dry weight percentage or (w/v).Regarding exemplary embodiments of biocompatible composition disclosedherein, some include one or more additives present at predefined ratiorange of about 0.001, 0.01, 0.1, 1, 5, 10, 20, 30 or 40% by dry weightpercentage or (w/v) to from about 40, 50, 60, 70, 80, 90, 95 or 99% bydry weight percentage or (w/v). In suitable embodiments, the one or moreadditives are present in an amount from about 0.1% by dry weightpercentage or (w/v) to about 10% by dry weight percentage or (w/v). Inother embodiments, an additive is not a component of the biocompatiblecomposition of the indicator.

In some embodiments, at least one solvent is employed at a predefinedratio or concentration in the biocompatible composition at a range ofabout 0.001, 0.01, 0.1, 1, 5, 10, 20, 30 or 40% by dry weight percentageor (w/v) to from about 40, 50, 60, 70, 80, 90, 95 or 99% by dry weightpercentage or (w/v). In suitable embodiments, the at least one solventis present in an amount from about 0.1% by dry weight percentage or(w/v) to about 60% by dry weight percentage or (w/v). In otherembodiments, a solvent is not a component of the biocompatiblecomposition of the indicator. Concentrations or predefined ratios of theone or more fillers, binders, additives and solvents are alsodetermined, in certain embodiments, such that the intended properties ofthe resulting biocompatible composition and indicator regions are inaccord with the intended use of the present disclosure. The skilledartisan will readily recognize that various concentrations andcombinations of the foregoing materials can be applied for a desireduse.

Insofar as the biocompatible compositions forming the indicator region,material, layer, composition, component, and the like, is a materialcomponent of the device itself, i.e., it is coterminous with thestructure of the device, and/or are permanently attached, adhered orcoupled to the devices of the present disclosure, e.g., as anindependently affixed layer by a surface application process, suchdevices in suitable embodiments are selected from, but not limited to,single use surgical devices, orthopedic surgical devices, reamers, awls,rod benders, drill guides, guide tubes, distance gages, inserters,implant holders, clamps, portals, screwdrivers, spacers, distracters,plate benders, broaches, fusion plates, fusion screws, spinal rods,spinal connectors, artificial discs, tissue-anchoring devices, fixationdevices, Stineman pins, dilators, joint spreaders, rasps, fusion cages,Kerrisons and Rongeurs, and combinations thereof.

In this regard, the devices of the present invention typically have aproximal end and a distal end, where, for example, the distal end of thedevice or instrument is the functional region that, in illustrativeembodiments, contacts the area of the patient being operated on, e.g.,the distal end is typically not the device region contacted by theclinician or surgeon. The proximal end, on the other hand, for example,is the structural region that, in illustrative embodiments, is contactedby the clinician or surgeon, which typically does not come into contactwith a patient's bodily fluids, e.g., blood. In illustrativeembodiments, the proximal end of the device is the region that, at leastin part, is composed of or harbors the single-use indicators disclosedherein. Some embodiments of the present invention, however, provide forvarious, additional and/or alternative locations on the medical devicethat encompasses an indicator region.

In illustrative embodiments, the modified state of the at least oneindicator region irreversibly identifies that the medical device hasbeen subjected to the exposure after the single procedure, and whereinthe exposure entails subjecting the medical device including the atleast one indicator region to water contact, where the contact withwater is selected from disinfection, washing, sterilizing, steamsterilization, and/or one or more autoclave cycles. In suitableembodiments, the medical device has a proximal end and a distal end, andwhere the at least one indicator region is positioned at or about theproximal end of the medical device. In suitable embodiments, theproximal end of the device and/or the indicator region is sufficientlylocated, configured, arranged and/or positioned on, or with respect to,the medical device such that the indicator region and/or proximal end ofthe device is not subjected to an exposure until after the singleprocedure.

To the extent that the biocompatible compositions forming the indicatorregion, material, layer, composition, component, and the like, arepermanently attached, adhered or coupled to the devices of the presentdisclosure, e.g., as an independently affixed layer by a surfaceapplication process, such a layer, in some embodiments can be one ormore layers. Nevertheless, the one or more layers of the biocompatiblecompositions forming the indicator region are applied to the device, asdetailed herein, at a depth or thickness. The depth or thickness of theindicator surface layer, in illustrative embodiments, is from about0.001, 0.01, 0.1, 1, 0.25, 0.5, 0.75, 1, 3, 5, 7, 9, 10, 15, 20, 30, 50,100, 500, or 900 nm, μm or mm to about 0.1, 0.25, 0.5, 0.75, 1, 3, 5, 7,9, 10, 15, 20, 30, 50, 100, 500, or 900 nm, μm or mm. In otherembodiments, the depth or thickness is from about 0.001, 0.01, 0.1, 1,0.25, 0.5, 0.75, 1, 3, 5, 7, 9, or 10 nm, μm or mm to from about 0.5,0.75, 1, 3, 5, 7, 9, 10, 15, 20, 30, 50, or 100 nm, μm or mm. Insuitable embodiments, the depth or thickness of the layer is about 10 μmto 3 mm.

In illustrative embodiments, the biocompatible composition is formulatedsuch that after the biocompatible composition is applied to a proximalend of a device, i.e., constituting the indicator region, thesuperabsorbent polymer (SAP) is sterically arrange throughout theindicator region to ensure that water, when present, is able tocontact—and accordingly swell—the SAP, i.e., the water is accessible tothe SAP for adsorption via SAP surface exposure. Likewise, in someembodiments of the present invention, the SAP molecules are contiguouslyconformed or are arranged in a substantially contiguous configurationwithin the biocompatible composition, and consequently throughout theindicator region, such that water, when present, is able to continuouslypercolate the indicator region until the SAP swelling capacity isachieved.

Single Procedure Indicator Methods and Applications

In one aspect, the present disclosure provides a method of manufacturinga single procedure device indicator, entailing (a) selecting a medicaldevice; (b) preparing the indicator, where the indicator is abiocompatible composition with at least one filler and one or morebinders that are present in the biocompatible composition at apredefined ratio by weight percentage, and (c) applying thebiocompatible composition to the medical device to form at least oneindicator region, where the at least one indicator region is configuredto transition from an unmodified state to a modified state in responseto an exposure. In illustrative embodiments the modified state of the atleast one indicator region irreversibly identifies that the medicaldevice has been subjected to the exposure after the single procedure.

The biocompatible composition is prepared in some embodiments by mixingtogether the at least one filler and the one or more binders at thepredefined ratios detailed herein. In certain embodiments, thebiocompatible composition further includes one or more solvents,additives, accelerants, surfactants, emulsifiers, reducing agents,fluidizing agents, detergents, wetting agents, and dispersants, andcombinations thereof. These components, in various combinations andconcentrations, i.e., appropriate for forming the compositions andindicators of the present invention, are combined or mixed at atemperature, pH, gas concentration, e.g., O₂, CO₂, nitrogen levels,etc., salinity, ionic concentration, etc., and for a duration of timesufficient to produce an indicator slurry, solution, emulsion, sols,gel, semi-solid, gel-sol, aggregate composition, paste, material, paint,coating, dip coating, and the like, capable of transiting from theunmodified state to the modified state in response to the exposure.

For example, some embodiments of the present invention include, but arenot limited to, providing a filler solution of about 30-90 by weightpercentage in the biocompatible composition, where the fillercomposition or solution is combined with a binder composition orsolution, for example, in some embodiments, one or more binders in asolvent, of about 10-70 by weight percentage of the binder compositionor solution in the biocompatible composition at room temperature (RT)for about 5 minutes to about 3 hours with stirring. Additionally oralternatively the foregoing solutions and/or compositions may alsocontain one or more additives that are present at a range of about0.1-10 by weight percentage in the biocompatible composition, while someembodiments further entail one or more suitable solvents at a range ofabout 0.1-60 by weight percentage in the biocompatible composition.

The present mixtures are combined, reacted, mixed, etc., for asufficient time, at an appropriate temperature to produce a formulationwith the desired physical and chemical properties, e.g., viscosity,purity, adherence, boiling point, density, osmotic polarity, colloidalconsistency, hydrophilicity, hydrophobicity, etc., to ensure that,depending on the intended application as described herein, thebiocompatible composition of the indicator region is capable offunctioning as a component or constituent of a device, i.e., it isconfigured to transition from an unmodified state to a modified state inresponse to an exposure.

The slurries, solutions, emulsions, sols, gels, semi-solids, gel-sols,aggregate compositions, pastes, materials, paints, coatings, dipcoatings, and the like, of the present invention are also subjected toother processes and techniques to achieve the desired compositecharacteristics of the present biocompatible composition of theindicator region or material. Some of these processes and techniques,include, but are not limited to, subjecting the foregoing mixtures toone or more of centrifugation, drying, desiccating, buffering,chromatography, exchange resin chromatography, size exclusionchromatography, concentration, dilution, distillation, heating, cooling,suspending, reacting, precipitating, homogenizing, saturating,unsaturation techniques, and solubilizing, and the like, andcombinations thereof.

Methods for producing the biocompatible composition of the indicatoralso include, in certain embodiments, mixing one or more of the fillers,binders, additives and/or solvents to form a congealed matrix orotherwise suitable biocompatible composition state. In this regard,illustrative embodiments of the present disclosure provide for a filler,binder, additive, and/or solvent mixture at a final concentration fromabout 0.001, 0.01, 0.1, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 10, 20, 30,40, 50, 60, 70, 80 or 90% (w/v) of the filler, binder, additive, and/orsolvent mixture to from about 1, 5, 10, 20, 30, 40, 50, 60, 70 80, 90 or9% (w/v) of the filler, binder, additive, and/or solvent mixture.

Mixing the one or more fillers, binders, additives, and/or solvents intoa slurry or solution at a final concentration can be performed byvarious methods known in the art. It will be readily apparent to theskilled artisan that heating a mixture, slurry, and/or solution to about30, 40, 50, 60, 70, 80, 90, 100, 110, 120, or 130° F. or ° C., or highertemperatures, for about 5-60 minutes min or hours will, thereby,sufficiently mix, disperse, and/or dissolve the one or more fillers,binders, additives, and/or solvents. In illustrative embodiments, aftermixing the foregoing components the final mixture, slurry and/orsolution is subsequently cooled to room temperature.

The pH of the mixture, slurry and/or solutions of the present disclosureis, in suitable embodiments, sufficient to facilitate the generation ofa biocompatible composition of the indicator region interactions. Inillustrative embodiments, the pH ranges from about 1, 2, 3, 4, 5, 6, 7or 8 to from about 5, 6, 7, 8, 9, 10, 11, 12, 13 or 14. In someembodiments, the pH ranges from about 5, 6, 7 or 8 to from about 6, 7, 8or 9. In illustrative embodiments, the pH is about 7 or 7.4, i.e.,physiological pH.

The polymers, materials, compositions and/or hydrogels of the presentdisclosure are allowed to properly congeal, in some embodiments, inorder to facilitate a suitable composition to function as the indicator.In illustrative embodiments, the polymers and/or hydrogels are allowedto congeal for about 0.001, 0.01, 0.1, 0.5, 1, 2, 3, 4, 5, 6, 7, 8, 9,10, 20, 30, or 50 hours (h). It will be readily apparent to the skilledartisan that numerous additional variables can effect polymerization,solidification, or congealing. Such factors include, for example,hydration, humidity, gas concentration, and/or temperature, etc. Theskilled artisan will readily appreciate that appropriate adjustments canoptimize indicator production for specific or desired uses.

The respective biocompatible compositions and/or surface layers have auniform thickness, in some embodiments, when applied to a device or as acomponent of the device. In addition, the respective compositions layersmay be formed of the same or different materials. In suitableembodiments, it is preferred that the respective compositions and/orsurface layers be formed of the same material with the same thickness.In such configuration, a temperature, pressure and/or water stress,e.g., an exposure, may be uniformly applied on part or all surfaces ofthe device substrate. In some embodiments, one or more layers of thebiocompatible compositions are applied to a device or instruments toform the indicator region.

In illustrative embodiments, the biocompatible composition is formulatedsuch that after the biocompatible composition is applied to a proximalend of a device, i.e., constituting the indicator region, thesuperabsorbent polymer (SAP) is sterically arrange throughout theindicator region to ensure that water, when present, is able tocontact—and accordingly swell—the SAP, i.e., the water is accessible tothe SAP for adsorption via SAP surface exposure. Likewise, in someembodiments of the present invention, the SAP molecules are contiguouslyconformed or are arranged in a substantially contiguous configurationwithin the biocompatible composition, and consequently throughout theindicator region, such that water, when present, is able to continuouslypercolate the indicator region until the SAP swelling capacity isachieved.

Certain embodiments of the present invention include methods of applyingthe biocompatible compositions of the indicator material as a coating ordip coating by using a slurry or suspension of the desired fillers,binders, additive and/or solvents. The steps of the method entail, insome embodiments, preparing a solution or suspension consistingessentially of a coating component, where the coating component consistsessentially of the biocompatible composition constituents, which yieldacceptable results. In suitable embodiments, the medical device has aproximal end and a distal end, and where the at least one indicatorregion is positioned at or about the proximal end of the medical device.In suitable embodiments, the proximal end of the device and/or theindicator region is sufficiently located, configured, arranged and/orpositioned on, or with respect to, the medical device such that theindicator region and/or proximal end of the device is not subjected toan exposure until after the single procedure.

In this particular embodiment, the resulting slurry is poured into thedip-coating container and a desired region of a surgical or medicaldevice, e.g., the proximal region, is subsequently submerged into theslurry via a dip-coater or appropriate, e.g., Instron apparatus (dippingstep), in illustrative embodiments. At a withdrawal rate of, for exampleonly, 0.0762 cm/s, the coated device or region is removed from theslurry and allowed to air dry before subjecting the coated region to adrying step, in suitable embodiments. The coated region is then allowedto cool and additional coatings may be added by repeating the dippingand drying steps in various embodiments.

In accord with its application, after applied to the device orinstrument at the proximal end and stabilizes, in illustrativeembodiments, the biocompatible composition is now effectively theindicator region as described herein. As such, the indicator region,prior to any exposure, is present in the unmodified state. In thisregard, such a device or instrument having or harboring an unmodifiedindicator region, has not been discharged to the extent that anaffirmative discharge status requires first (i) a single-use, and (ii) awater, e.g., steam sterilization, exposure to transition the unmodifiedstate to the modified state. Nevertheless, the indicator regionpossesses the ability, in some embodiments, to transition from theunmodified state to the modified state after an exposure. In suitableembodiments, the exposure comprises subjecting the medical deviceincluding the at least one indicator region to one or more autoclavecycles.

In illustrative embodiments, the exposure entails subjecting the medicaldevice including the at least one indicator region to the presence ofwater, where in certain embodiments, the water presence occurs via oneor more autoclave steam sterilization cycles. In suitable embodiments,the one or more steam sterilization cycles are performed for a durationat temperatures and pressures sufficient to (i) transition the at leastone indicator region from the unmodified state to the modified state,and (ii) sterilize the device, as previously discussed. With respect tothe indicator region per se, the transition to the modified state isreadily apparent, visually and/or in a tactile manner, to an observerdue to the dramatic increase in volume, e.g., via hydration, swelling orattaining its swelling capacity, of the superabsorbent polymer materialas discussed above.

Similarly, another aspect of the present disclosure provides a methodfor determining the discharge status of a single procedure device,including (a) providing the device, where the device includes at leastone indicator region configured to transition from an unmodified stateto a modified state in response to an exposure, (b) subjecting thedevice to the exposure after the single procedure has been performedusing the device, (c) assessing the transition state of the at least oneindicator region, where the modified state of the at least one indicatorregion irreversibly identifies that the device has been subjected to theexposure after the single procedure, and (d) determining the dischargestatus of the device based on the transition state assessment of the atleast one indicator region, where the device is affirmatively dischargedwhen the at least one indicator region is in the modified state.

Certain embodiments, moreover, entail an irreversible identificationwith respect to the transition of the indicator region to the modifiedstate, where the irreversible identification is a visual and tactileidentification. In some embodiments, the modified state of the at leastone indicator region renders the device clinically impractical for reusedue to the morphological consistency of the indicator region when in themodified state. In certain embodiments the one or more superabsorbentpolymers is sodium polyacrylate, where the sodium polyacrylate possessesa degree of ionization ranging from about 30-100 percent. In someembodiments, the at least one indicator region includes a biocompatiblecomposition entailing one or more of (i) at least one filler, (ii) oneor more binders, (iii) one or more additives, and (iv) a solvent, andcombinations thereof.

In illustrative embodiments, the methods further entail one or more of(e) labelling the affirmatively discharged device as end-of-use, (f)segregating the affirmatively discharged device from other singleprocedure devices that have not been affirmatively discharged, and/or(e) disposing of the affirmatively discharged device. In someembodiments, the exposure comprises subjecting the device including theat least one indicator region to a water treatment, e.g., but notlimited to, one or more steam sterilization cycles. In suitableembodiments, the one or more steam sterilization cycles are performedfor a duration at temperatures and pressures sufficient to (i)transition the at least indicator region from the unmodified state tothe modified state, and (ii) sterilize the device.

The biocompatible composition of the indicator, in illustrativeembodiments, consists of sodium polyacrylate as a non-limiting filler ina system, method or composition entailing a binder selected from alkyds,acrylic, vinyl-acrylics, polyurethanes, polyesters, melamine, epoxy,silanes, siloxanes and/or oils. In some embodiments where a solvent isemployed, xylene, toluene, an alcohols or a ketones is selected inaddition to or as an alternative to one or more additives, such as, butnot limited to clays, kaolin, kaolinite, halloysite, diaspore, bentonite(Fuller's earth), ball clay, common clay, shale, fire clay, illite,chlorite, smectite minerals, quartz, limestone, silicate compounds, andquartz, and/or combinations thereof, to improve the mechanicalproperties and/or stabilize the compositions of the present invention.

When sodium polyacrylate is selected as the superabsorbent polymer, theweight percentage in biocompatible composition of the indicator is fromabout 30-90 percent. Along the same lines, when the binder is selectedfrom an alkyd, acrylic, vinyl-acrylics, polyurethanes, polyesters,melamine, epoxy, silanes, siloxanes and/or oils, weight percentage inbiocompatible composition of the indicator is from about 10-70 percent.Solvents such as xylene, toluene, an alcohol or a ketone, when used inthe methods, systems and compositions herein, are present at a weightpercentage in biocompatible composition of the indicator is from about0.0001-99 percent. Likewise, when the indicator materials andcompositions contain an additive such as clays, kaolin, kaolinite,halloysite, diaspore, bentonite (Fuller's earth), ball clay, commonclay, shale, fire clay, illite, chlorite, smectite minerals, quartz,limestone, silicate compounds, and quartz, the weight percentage in thebiocompatible composition of the indicator is from about 0.0001-99percent to from about 0.1-10 percent.

Some or all of the foregoing ranges were assessed and found to beexemplary by empirical determination, while some or all of the foregoingranges relate to the chemical or physical constraints of the compositionconstituents. For example, in one embodiment, a lower range as detailedabove may relate to the particle size of the filler, e.g., sodiumpolyacrylate, binder, additives, solvents, etc. The upper limit in thiscontext relates to, in some embodiments, the hydrated or swollen sodiumpolyacrylate in addition to or alternative with the binder, solvent andadditive, where sizes greater than the disclosed ranges above mayaggregate, precipitate out of solution and/or disengage from the device.In some embodiments, the range of ionization for sodium polyacrylate isabout from 30-100%.

FIG. 2 shows an illustrative embodiment of the present invention. In anoperation 100, a medical device composed of plastic proximal end 110,conduit region 120, and distal end 130 is provided. In operation 100,plastic proximal end 110 is coated with an unmodified indicator 140 andexposed to water, which, in the present operation, is a steamsterilization procedure 150. In operation 100, steam sterilizationprocedure 150 transforms unmodified indicator 140 to the modifiedindicator 160.

EXAMPLES

The present compositions and methods will be understood more readily byreference to the following examples, which are provided by way ofillustration and are not intended to be limiting in any way.

Example 1 Preparation Polymer Matrices

Superabsorbent polymer matrices. The superabsorbent polymer matriceswere prepared by mixing sodium polyacrylate with one or more alkyds,acrylics, vinyl-acrylics, polyurethanes, polyesters, melamine, epoxy,silanes, siloxanes and oils, as the binding agent. Separate examplesincluded one or more additives, e.g., clay (kaolin), limestone andquartz, to structurally stabilize the mixture, where an appropriatesolvent, such as, xylene, toluene, an alcohol, or ketones were alsoemployed in other examples.

The respective compositions, by weight percentage in the mixture, of thesodium polyacrylate, at a molecular weight of 100 to 3,000 kg/mol,binder, solvent (when included), and additives (when included) were30-90, 10-70, 0.1-60, and 0.1-10 percent. The degree of sodiumpolyacrylate ionization ranged from 30-100 percent in these examples.The composition was prepared by mixing together the sodium polyacrylateand binder (with additives and/or a solvent, when included) at theconcentrations noted above to produce a hydrogel slurry that wasaccordingly applied to the proximal end of a medical device at athickness of 100 μm to 3 mm, which respectively corresponded to theparticle size of sodium polyacrylate prior to water exposure and thehydrated sodium polyacrylate that was subsequently exposed to steamsterilization and/or water.

Example 2 Mechanism of Water-Absorbing Polymers

Water absorbing polymers that were used are superabsorbentmacromolecules, which contain hydrophilic backbones. These polymerscontain carboxylic acid and carboxylate ion groups, which indicated afavorable interaction with the water molecules. These electrostatichydrogen bond interactions occurred between the electronegative oxygenatoms and electron deficient hydrogen atoms as shown in FIG. 1, which isan exemplary representation of such intermolecular interactions betweenthe polymer matrix functional groups and water molecules. FIG. 1A, tothis end, shows the hydrogen bonding between polymer matrix carboxylicacid groups and water molecules, while FIG. 1B depicts hydrogen bondingbetween the carboxylate ion group groups of the polymer matrix and watermolecules. The hydrogen bonding interactions thereby decreased theenergy of the system. And, moreover, while the hydrophilic polymerchains of the superabsorbent matrix have the tendency to disperse in anaqueous solution, thereby allowing for various morphologicalconfigurations—and thus increasing the entropy of the system—the polymerchains were cross-linked to form a three dimensional network. In thisrespect, the resulting three dimensional network structure, althoughallowing for swelling of the superabsorbent matrix, it precludes watermolecule dissemination. Accordingly, the prepared indicationcompositions of this example were irreversible.

Example 3 SAPs as Sterilization Indicators

A single procedure intramedullary reamer was obtained, which consists ofa plastic cylindrical component located at its proximal end, i.e.,around the shaft. In this example, the plastic part (or portions of itin separate examples) was coated with sodium polyacrylate, abiocompatible superabsorbent polymer. As a result, when exposed towater, via a steam sterilization procedure, the polymer material swelledsignificantly and became pliable. The swelling persisted even after thedevice indicator region was removed from the steam environment detailedbelow. FIG. 2 to this end entails a schematic representation of thesingle-use indicator on the single procedure reamer prior to andfollowing water exposure, e.g., via steam sterilization.

FIG. 3 further details the single-use superabsorbent polymer indicator,sodium polyacrylate, which, in this instance, was not applied to adevice, in two separate pouches prior to and following steamsterilization. FIG. 3A shows the sodium polyacrylate-based indicatorbefore being subjected to steam sterilization, while FIG. 3B is aphotograph of the sodium polyacrylate-based indicator after steamsterilization. Briefly, the sodium polyacrylate compositions were placedin an open pouch of porous polypropylene, which was subsequently heatsealed to enclose the superabsorbent polymer. The two bags underwent atypical steam sterilization cycle, i.e., one gravity autoclave cycle at274° F. for 18 minutes followed by 20 minutes of drying. As shown in theFIG. 3 photographs, the pouches before and after steam sterilizationwere respectively in an unmodified and modified state. Thesuperabsorbent sodium polyacrylate polymer inside the pouch swelled to asignificant extent and the swelling was retained after the procedure.

FIG. 4 further details the single-use sodium polyacrylate polymerscoated on the proximal end of a medical device reamer prior to andfollowing water exposure. FIG. 4A shows the coated sodium polyacrylateindicator before water exposure, where FIG. 4B is a photograph of thecoated sodium polyacrylate indicator after such exposure. Here, thesodium polyacrylate composition was coated on a reamer shaft with anadhesive. Upon water exposure, the coated sodium polyacrylatecomposition indicator was swelled significantly to a soft, pliable,consistency. The results shown in FIG. 3 and FIG. 4 clearly demonstratethe utility of superabsorbent polymers as indicators for steamsterilization.

The present disclosure is not to be limited in terms of the particularembodiments described in this application. Many modifications andvariations can be made without departing from its spirit and scope, aswill be apparent to those skilled in the art. Functionally equivalentmethods and apparatuses within the scope of the disclosure, in additionto those enumerated herein, will be apparent to those skilled in the artfrom the foregoing descriptions. Such modifications and variations areintended to fall within the scope of the appended claims. The presentdisclosure is to be limited only by the terms of the appended claims,along with the full scope of equivalents to which such claims areentitled. It is to be understood that this disclosure is not limited toparticular methods, reagents, compounds compositions or biologicalsystems, which can, of course, vary. It is also to be understood thatthe terminology used herein is for the purpose of describing particularembodiments only, and is not intended to be limiting.

In addition, where features or aspects of the disclosure are describedin terms of Markush groups, those skilled in the art will recognize thatthe disclosure is also thereby described in terms of any individualmember or subgroup of members of the Markush group.

As will be understood by one skilled in the art, for any and allpurposes, particularly in terms of providing a written description, allranges disclosed herein also encompass any and all possible subrangesand combinations of subranges thereof. Any listed range can be easilyrecognized as sufficiently describing and enabling the same range beingbroken down into at least equal halves, thirds, quarters, fifths,tenths, etc. As a non-limiting example, each range discussed herein canbe readily broken down into a lower third, middle third and upper third,etc. As will also be understood by one skilled in the art all languagesuch as “up to,” “at least,” “greater than,” “less than,” and the likeinclude the number recited and refer to ranges which can be subsequentlybroken down into subranges as discussed above. Finally, as will beunderstood by one skilled in the art, a range includes each individualmember. Thus, for example, a group having 1-3 polymers refers to groupshaving 1, 2, or 3 polymers. Similarly, a group having 1-5 polymersrefers to groups having 1, 2, 3, 4, or 5 polymers, and so forth.

While various aspects and embodiments have been disclosed herein, otheraspects and embodiments will be apparent to those skilled in the art.The various aspects and embodiments disclosed herein are for purposes ofillustration and are not intended to be limiting, with the true scopeand spirit being indicated by the following claims.

All references cited herein are incorporated by reference herein intheir entireties and for all purposes to the same extent as if eachindividual publication, patent, or patent application was specificallyand individually incorporated by reference in its entirety for allpurposes.

What is claimed is:
 1. A method for determining the discharge status ofa single procedure device, comprising: (a) providing the device, whereinthe device includes at least one indicator region configured totransition from an unmodified state to a modified state in response toan exposure wherein said indicator region comprises a biocompatiblecomposition including one or more superabsorbent polymers possessing aswelling capacity range of about 30-500 fold the volume of the one ormore superabsorbent polymers prior to being subject to exposure; (b)subjecting the device to the exposure after the single procedure hasbeen performed using the device; (c) assessing the transition state ofthe at least one indicator region, wherein the modified state of the atleast one indicator region irreversibly identifies by swelling of saidone or more superabsorbent polymers that the device has been subjectedto the exposure after the single procedure; and (d) determining thedischarge status of the device based on the transition state assessmentof the at least one indicator region, wherein the device isaffirmatively discharged when the at least one indicator region is inthe modified state.
 2. The method of claim 1, further comprising one ormore of: (a) labelling the affirmatively discharged device as endof-use; (b) segregating the affirmatively discharged device from othersingle procedure devices that have not been affirmatively discharged;and (c) disposing of the affirmatively discharged device.
 3. The methodof claim 1, wherein the exposure comprises the device including the atleast one indicator region to (i) the presence of water, or (ii) one ormore steam sterilization cycles, or both.
 4. The method of claim 1,wherein the device is a single-use medical device comprising a proximalend and a distal end, and wherein the at least one indicator region islocated at or about the proximal end of the medical device.
 5. Themethod of claim 1, wherein the biocompatible composition furthercomprises one or more binders, one or more additives, and a solvent, andcombinations thereof.
 6. The method of claim 5, wherein the one or moresuperabsorbent polymer is present at a range of about 30-90 by weightpercentage in the biocompatible composition.
 7. The method of claim 6,wherein the one or more superabsorbent polymers are selected from thegroup consisting of polyacrylates, polyacrylamides, polyacrylamidecopolymers, polyacrylic acid, sodium polyacrylate, potassiumpolyacrylate, lithium polyacrylate, ammonium polyacrylate, ethylenemaleic anhydride copolymer, carboxymethylcellulose, polyvinyl alcoholcopolymers, polyethyleneoxide, and copolymers of polyacrylonitrile, andcombinations thereof.
 8. The method of claim 7, wherein the one or moresuperabsorbent polymers is sodium polyacrylate, and wherein the sodiumpolyacrylate possesses a degree of ionization ranging from about 30-100percent.
 9. The method of claim 5, wherein the one or more binders arepresent at a range of about 10-70 by weight percentage in thebiocompatible composition, and wherein the one or more binders areselected from the group consisting of alkyds, acrylics, vinyl-acrylics,polyurethanes, polyesters, melamine, epoxies, silanes, siloxanes, andoils, and combinations thereof.
 10. The method of claim 5, wherein theone or more additives are present at a range of about 0.1-10 by weightpercentage in the biocompatible composition, and wherein the one or moreadditives are selected from the group consisting of clays, kaolin,limestone, silicate compounds, and quartz, and combinations thereof. 11.The method of claim 5, herein the one or more solvents are present at arange of about 0.1-60 by weight percentage in the biocompatiblecomposition, and wherein the one or more solvents are selected from thegroup consisting of xylene, toluene, alcohols, and ketones, andcombinations thereof.